Increasing Brain Gamma Activity Improves Episodic Memory and Restores Cholinergic Dysfunction in Alzheimer's Disease

Annals of Neurology, Journal Year: 2022, Volume and Issue: 92(2), P. 322 - 334

Published: May 24, 2022

This study aimed to assess whether non-invasive brain stimulation with transcranial alternating current at gamma-frequency (γ-tACS) applied over the precuneus can improve episodic memory and modulate cholinergic transmission by modulating cerebral rhythms in early Alzheimer's disease (AD).In this randomized, double-blind, sham controlled, crossover study, 60 AD patients underwent a clinical neurophysiological evaluation including assessment of pre post minutes treatment γ-tACS targeting or tACS. In subset 10 patients, EEG analysis individualized modelling electric field distribution were carried out. Predictors efficacy evaluated.We observed significant improvement Rey Auditory Verbal Learning (RAVL) test immediate recall (p < 0.001) delayed scores after but not Face-name associations improved Short latency afferent inhibition, an indirect measure transmission, increased only 0.001). ApoE genotype baseline cognitive impairment best predictors response γ-tACS. Clinical correlated increase gamma frequencies posterior regions amount predicted precuneus.Precuneus γ-tACS, able γ-power activity on regions, showed performances, along restoration intracortical excitability measures transmission. Response was dependent genetic factors stage. ANN NEUROL 2022;92:322-334.

Language: Английский

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The role of gamma oscillations in central nervous system diseases: Mechanism and treatment

Frontiers in Cellular Neuroscience, Journal Year: 2022, Volume and Issue: 16

Published: July 29, 2022

Gamma oscillation is the synchronization with a frequency of 30-90 Hz neural oscillations, which are rhythmic electric processes neuron groups in brain. The inhibitory interneuron network necessary for production gamma but certain disruptions such as brain inflammation, oxidative stress, and metabolic imbalances can cause this to malfunction. oscillations specifically control connectivity between different regions, crucial perception, movement, memory, emotion. Studies have linked abnormal conditions central nervous system, including Alzheimer's disease, Parkinson's schizophrenia. Evidence suggests that entrainment using sensory stimuli (GENUS) provides significant neuroprotection. This review discusses function advanced activities from both physiological pathological standpoint, it emphasizes potential therapeutic approach range neuropsychiatric diseases.

Language: Английский

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A ubiquitous spectrolaminar motif of local field potential power across the primate cortex

Nature Neuroscience, Journal Year: 2024, Volume and Issue: 27(3), P. 547 - 560

Published: Jan. 18, 2024

Abstract The mammalian cerebral cortex is anatomically organized into a six-layer motif. It currently unknown whether corresponding laminar motif of neuronal activity patterns exists across the cortex. Here we report such in power local field potentials (LFPs). Using probes, recorded LFPs from 14 cortical areas hierarchy five macaque monkeys. locations recordings were histologically identified by electrolytic lesions. Across all areas, found ubiquitous spectrolaminar pattern characterized an increasing deep-to-superficial layer gradient high-frequency peaking layers 2/3 and superficial-to-deep alpha-beta 5/6. Laminar additional species showed that highly preserved among primates—macaque, marmoset human—but more dissimilar mouse. Our results suggest existence canonical layer-based frequency-based mechanism for computation.

Language: Английский

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Fast-spiking parvalbumin-positive interneurons in brain physiology and Alzheimer’s disease

Molecular Psychiatry, Journal Year: 2023, Volume and Issue: 28(12), P. 4954 - 4967

Published: July 7, 2023

Abstract Fast-spiking parvalbumin (PV) interneurons are inhibitory with unique morphological and functional properties that allow them to precisely control local circuitry, brain networks memory processing. Since the discovery in 1987 PV is expressed a subset of fast-spiking GABAergic neurons, our knowledge complex molecular physiological these cells has been expanding. In this review, we highlight specific neurons fire at high frequency reliability, enabling network oscillations shape encoding, consolidation retrieval memories. We next discuss multiple studies reporting neuron impairment as critical step neuronal dysfunction cognitive decline mouse models Alzheimer’s disease (AD). Finally, propose potential mechanisms underlying AD argue early changes activity could be causal AD-associated significant contributor pathogenesis.

Language: Английский

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Alzheimer’s disease: insights into pathology, molecular mechanisms, and therapy

Protein & Cell, Journal Year: 2024, Volume and Issue: unknown

Published: May 11, 2024

Abstract Alzheimer’s disease (AD), the leading cause of dementia, is characterized by accumulation amyloid plaques and neurofibrillary tangles in brain. This condition casts a significant shadow on global health due to its complex multifactorial nature. In addition genetic predispositions, development AD influenced myriad risk factors, including aging, systemic inflammation, chronic conditions, lifestyle, environmental exposures. Recent advancements understanding pathophysiology are paving way for enhanced diagnostic techniques, improved assessment, potentially effective prevention strategies. These discoveries crucial quest unravel complexities AD, offering beacon hope management treatment options millions affected this debilitating disease.

Language: Английский

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Dopamine neuron degeneration in the Ventral Tegmental Area causes hippocampal hyperexcitability in experimental Alzheimer’s Disease

Molecular Psychiatry, Journal Year: 2024, Volume and Issue: 29(5), P. 1265 - 1280

Published: Jan. 16, 2024

Abstract Early and progressive dysfunctions of the dopaminergic system from Ventral Tegmental Area (VTA) have been described in Alzheimer’s Disease (AD). During long pre-symptomatic phase, alterations function Parvalbumin interneurons (PV-INs) are also observed, resulting cortical hyperexcitability represented by subclinical epilepsy aberrant gamma-oscillations. However, it is unknown whether deficits contribute to brain AD. Here, using Tg2576 mouse model AD, we prove that reduced hippocampal innervation, due VTA dopamine neuron degeneration, impairs PV-IN firing gamma-waves, weakens inhibition pyramidal neurons induces via lower D2-receptor-mediated activation CREB-pathway. These coincide with numbers Perineuronal Net density. Importantly, L-DOPA selective D2-receptor agonist quinpirole rescue p -CREB levels improve PV-IN-mediated inhibition, thus reducing hyperexcitability. Moreover, similarly quinpirole, sumanirole – another a known anticonvulsant not only increases PV-INs but restores gamma-oscillations mice. Conversely, blocking transmission sulpiride (a D2-like receptor antagonist) WT mice reduces PV-INs, mimicking what occurs Tg2576. Overall, these findings support hypothesis integrity plays key role survival, disclosing relevant contribution tone epileptiform activity early

Language: Английский

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40 Hz light flickering promotes sleep through cortical adenosine signaling

Cell Research, Journal Year: 2024, Volume and Issue: 34(3), P. 214 - 231

Published: Feb. 8, 2024

Abstract Flickering light stimulation has emerged as a promising non-invasive neuromodulation strategy to alleviate neuropsychiatric disorders. However, the lack of neurochemical underpinning hampered its therapeutic development. Here, we demonstrate that flickering triggered an immediate and sustained increase (up 3 h after flickering) in extracellular adenosine levels primary visual cortex (V1) other brain regions, function frequency intensity, with maximal effects observed at 40 Hz 4000 lux. We uncovered cortical (glutamatergic GABAergic) neurons, rather than astrocytes, cellular source, intracellular generation from AMPK-associated energy metabolism pathways (but not SAM-transmethylation or salvage purine pathways), efflux mediated by equilibrative nucleoside transporter-2 (ENT2) molecular pathway responsible for generation. Importantly, 20 80 Hz) 30 min enhanced non-rapid eye movement (non-REM) REM sleep 2–3 mice. This somnogenic effect was abolished ablation V1 superior colliculus) neurons genetic deletion gene encoding ENT2 ENT1), but recaptured chemogenetic inhibition focal infusion into dose-dependent manner. Lastly, also promoted children insomnia decreasing onset latency, increasing total time, reducing waking onset. Collectively, our findings establish ENT2-mediated signaling basis flickering-induced unravel novel treatment insomnia, condition affects 20% world population.

Language: Английский

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Translation of neurotechnologies

Nature Reviews Bioengineering, Journal Year: 2024, Volume and Issue: 2(8), P. 637 - 652

Published: May 31, 2024

Language: Английский

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Photobiomodulation for Alzheimer’s Disease: Has the Light Dawned?

Photonics, Journal Year: 2019, Volume and Issue: 6(3), P. 77 - 77

Published: July 4, 2019

Next to cancer, Alzheimer's disease (AD) and dementia is probably the most worrying health problem facing Western world today. A large number of clinical trials have failed show any benefit tested drugs in stabilizing or reversing steady decline cognitive function that suffered by patients. Although pathological features AD consisting beta-amyloid plaques tau tangles are well established, considerable debate exists concerning genetic lifestyle factors predispose individuals developing dementia. Photobiomodulation (PBM) describes therapeutic use red near-infrared light stimulate healing, relieve pain inflammation, prevent tissue from dying. In recent years PBM has been applied for a diverse range brain disorders, frequently non-invasive manner shining on head (transcranial PBM). The present review discusses mechanisms action tPBM brain, summarizes studies used treat animal models AD. results limited patients with discussed.

Language: Английский

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Evolution of neuroinflammation across the lifespan of individuals with Down syndrome

Brain, Journal Year: 2020, Volume and Issue: 143(12), P. 3653 - 3671

Published: Sept. 10, 2020

Epidemiological and experimental studies suggest that a disease-aggravating neuroinflammatory process is present at preclinical stages of Alzheimer's disease. Given individuals with Down syndrome are increased genetic risk disease therefore develop the spectrum neuropathology in uniform manner, they constitute an important population to study evolution neuroinflammation across continuum. Therefore, this cross-sectional study, we characterized brain inflammatory profile lifespan syndrome. Microglial morphology cytokine expression were analysed by immunohistochemistry electrochemiluminescent-based immunoassays frontal cortex from foetuses adults control subjects (16 gestational weeks 64 years), totalling 127 cases. Cytokine mixed foetal primary cultures hippocampus syndrome, as well effects sex on also analysed. A higher microglial soma size-to-process length ratio was observed children young before development full-blown pathology. Moreover, displayed numbers rod-like microglia. Increased levels interleukin-8 interleukin-10 (1-10 years; n = 5, controls 10) interleukin-1β, interleukin-1α, interleukin-6, interleukin-8, interleukin-10, interleukin-15, eotaxin-3, interferon gamma-induced protein 10, macrophage-derived chemokine, macrophage protein-beta, found compared euploid cases (13-25 years, 6, 24). conditioned media cortical second trimester (Down 7, 7). Older (39-68 22, 16) reduced interleukin-12p40, interferon-gamma tumour necrosis factor-alpha. Microglia larger somas shorter processes. increase dystrophic microglia aligning neurons harbouring tau pathology observed. Sex stratification analyses revealed females had interleukin-6 males Finally, multivariate projection methods identified specific patterns among Our findings indicate presence early evolving phenotype knowledge relevant for discovery stage-specific targets design possible anti-inflammatory trials against population.

Language: Английский

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